Dihaloadipates are important intermediates in the formation of many compounds having pharmaceutical, herbicidal and other attributes. In particular, the esterified derivatives of meso-2,5-dihaloadipates are useful intermediates in the synthesis of heterocycles such as disubstituted pyrrolidines and diazabicyclooctanes.
A number of methods directed to the synthesis of the meso compounds have been reported.
For instance, an article by Willstatter appearing in Chem. Ber., 35, 2065,1902 reports the synthesis of the diethylester of meso dibromoadipate with very little experimental detail.
In later articles appearing in J. Chem. Soc., 273, 1909 and J. Chem. Soc. 951, 1921, the bromination of the adipoyl halide and latter esterification to yield the diethyl ester resulted in yields of the desired product of 28% and 40%, respectively. The above two references disclose the improved formation of the meso-ester only after high temperature vacuum distillation.
An analogous process affording a 60% yield of the methyl ester of the dihalo adipoyl halide is reported in J. Org. Chem., 26, 2750, 1961. The method reported in this reference also required careful fractionation.
An article appearing in J. Amer. Chem. Soc. 64, 2696, (1942), discloses the preparation of meso methyl dibromoadipate in a 70% yield by (a) a first crop crystallization of 50% of pure meso and (b) fractional distillation of the resulting mother liquor to obtain the remaining 20% of the pure meso compound. These authors report that the diethyl ester was obtained in an overall yield of 46%.
Thus, there remains a need for a process affording the pure meso-2,5-dibromoadipate without resort to careful fractionation or long reaction times.